Rinehart et al. have recently reported on ecteinascidins (Et's) 729 (hydrated molecular weight, 747), 743 (761), 745. 759A,B (777). 770, and their derivatives O-methyl-Et 729 and O-methyl-Et 743. See for example, J. Orz. Chem., 1990, 55, 4512-4515; Topics in Pharmaceutical Sciences 1989, Amsterdam Medical Press, 1989, pp. 613-626; J. Nat. Prod., 1990, 53, 771-792; Biological Mass. Spectrometry, Elsevier 1990, pp. 233-258; and Pure Appl. Chem., 1990, 62, 1277-1280. Two of those compounds (Et 729, 743) have also been described by others. (See for example, Wright et al., J. Org. Chem., 1990, 55, 4508-4512).
The major component, ecteinascidin 743 (Et 743, (Rinehart et al.. J. Orz. Chem., 1990, 55, 4512-4515), and the others were assigned tris(tetrahydroisoquinoline) structures by correlation NMR techniques, as well as by fast atom bombardment (FAB)MS and tandem MS (FABMS/MS). Among these potent antitumor agents, Et 729 showed especially promising activities vs. tumor cells, but only minute quantities of pure sample were obtained. See for example, Rinehart et al., Topics in Pharmaceutical Sciences 1989 pp. 613-626, Amsterdam Medical Press B.V., The Netherlands, (1989), Holt et al., Diss. Abstr. Int. B. 47, 3771-3772 (1987) and Rinehart et al., U.S. Pat. Appln. Ser. No. 872,189, filed Jun. 9, 1986; PCT Intl. Appln. W087 07,610, filed Dec. 17, 1987; Chem. Abstr., 109, 811j, (1988).
The need for further biological evaluation promoted the development of a more efficient large-scale isolation procedure. During that process, two new biologically active ecteinascidins; Et 736 (754) and Et 722 (740), were isolated from Ecteinascidia turbinata samples collected at various locations in the Caribbean.